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Sofosbuvir + Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 or 3 Hepatitis C Infection Who Are Interferon Intolerant, Interferon Ineligible or Unwilling to Take Interferon (POSITRON)

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ClinicalTrials.gov Identifier: NCT01542788
Recruitment Status : Completed
First Posted : March 2, 2012
Results First Posted : February 17, 2014
Last Update Posted : May 19, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Hepatitis C
Interventions Drug: SOF
Drug: RBV
Drug: Placebo to match SOF
Drug: Placebo to match RBV
Enrollment 278
Recruitment Details Participants were enrolled at 54 sites in the North America, Australia, and New Zealand. The first participant was screened on 07 March 2012. The last participant observation was on 04 February 2013.
Pre-assignment Details 410 participants were screened and 280 were randomized. Of those participants randomized, 278 received at least one dose of study drug, and comprise the Safety Analysis Set and the Full Analysis Set.
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description Participants were randomized to receive sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations. Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Period Title: Overall Study
Started 209 71
Randomized and Treated 207 71
Completed 154 0
Not Completed 55 71
Reason Not Completed
Randomized but Not Treated             2             0
Lack of Efficacy             41             71
Lost to Follow-up             5             0
Death             3             0
Protocol Violation             2             0
Physician Decision             1             0
Withdrawal by Subject             1             0
Arm/Group Title SOF+RBV Placebo Total
Hide Arm/Group Description Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations. Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts. Total of all reporting groups
Overall Number of Baseline Participants 207 71 278
Hide Baseline Analysis Population Description
Participants in the Safety Analysis Set (randomized and received at least 1 dose of study drug) were analyzed for baseline characteristics.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 207 participants 71 participants 278 participants
52  (9.9) 52  (8.2) 52  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
Female
90
  43.5%
37
  52.1%
127
  45.7%
Male
117
  56.5%
34
  47.9%
151
  54.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
Hispanic or Latino
19
   9.2%
11
  15.5%
30
  10.8%
Not Hispanic or Latino
188
  90.8%
60
  84.5%
248
  89.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
American Indian or Alaska Native
2
   1.0%
0
   0.0%
2
   0.7%
Asian
7
   3.4%
1
   1.4%
8
   2.9%
Native Hawaiian or Other Pacific Islander
1
   0.5%
0
   0.0%
1
   0.4%
Black or African American
9
   4.3%
4
   5.6%
13
   4.7%
White
188
  90.8%
66
  93.0%
254
  91.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
United States 168 60 228
Canada 15 8 23
Australia 18 3 21
New Zealand 6 0 6
Cirrhosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
No 176 58 234
Yes 31 13 44
HCV Genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
Genotype 2 109 34 143
Genotype 3 98 37 135
IL28 Genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
CC 97 29 126
CT 84 36 120
TT 26 6 32
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 207 participants 71 participants 278 participants
6.3  (0.77) 6.3  (0.76) 6.3  (0.77)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
< 6 log10 IU/mL 67 17 84
≥ 6 log10 IU/mL 140 54 194
Interferon Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 71 participants 278 participants
Ineligible 88 33 121
Intolerant 17 8 25
Unwilling 102 30 132
1.Primary Outcome
Title Percentage of Participants Achieving SVR12
Hide Description SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy
Time Frame Post-treatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants with genotype 2 or 3 HCV infection who were randomized into the study and received at least 1 dose of study drug
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 207 71
Measure Type: Number
Unit of Measure: percentage of participants
78 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF+RBV, Placebo
Comments A sample size of 180 subjects in the active group and 60 in the placebo group would provide 99% power to detect a difference between group SVR12 rates of 40% using a 2-sided continuity-corrected chi-square test at significance level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments P-value is from the Cochran-Mantel-Haenszel test stratified by presence or absence of cirrhosis for the superiority of SOF+RBV over placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion difference
Estimated Value 77.3
Confidence Interval (2-Sided) 95%
71.0 to 83.6
Estimation Comments The difference in proportions between treatment groups and associated 95% confidence interval (CI) are calculated based on stratum-adjusted Mantel-Haenszel proportions.
2.Primary Outcome
Title Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug
Hide Description The number of subjects experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 207 71
Measure Type: Number
Unit of Measure: participants
No adverse event leading to discontinuation 202 68
Abdominal pain upper 1 0
Alanine aminotransferase increased 0 1
Anaemia 1 0
Anxiety 1 0
Chest discomfort 1 0
Injury 1 0
Insomnia 1 0
Muscle spasms 1 0
Oedema peripheral 0 1
Pancreatitis 0 1
Rash 0 1
Road traffic accident 1 0
3.Secondary Outcome
Title Percentage of Participants Achieving SVR4
Hide Description SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy
Time Frame Post-treatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 207 71
Measure Type: Number
Unit of Measure: percentage of participants
83.1 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF+RBV, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion difference
Estimated Value 82.7
Confidence Interval (2-Sided) 95%
76.8 to 88.5
Estimation Comments The difference in proportions between treatment groups and associated 95% CI are calculated based on stratum-adjusted Mantel-Haenszel proportions.
4.Secondary Outcome
Title Percentage of Participants Achieving SVR24
Hide Description SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy
Time Frame Post-treatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 207 71
Measure Type: Number
Unit of Measure: percentage of participants
77.8 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF+RBV, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments P-value is from the Cochran-Mantel-Haenszel test stratified by randomization stratification factor for the superiority of SOF+RBV over placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion difference
Estimated Value 77.3
Confidence Interval (2-Sided) 95%
71.0 to 83.6
Estimation Comments The difference in proportions between treatment groups and associated 95% CI are calculated based on stratum-adjusted Mantel-Haenszel proportions.
5.Secondary Outcome
Title Percentage of Participants Experiencing Viral Breakthrough
Hide Description Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 207 71
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0
6.Secondary Outcome
Title Percentage of Participants Experiencing Viral Relapse
Hide Description Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame End of treatment to post-treatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set who had an end-of-treatment response (HCV RNA < LLOQ as the last observed on-treatment value) were analyzed.
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description:
Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
Overall Number of Participants Analyzed 205 0
Measure Type: Number
Unit of Measure: percentage of participants
20.5
Time Frame Baseline to last dose date of study regimen + 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SOF+RBV Placebo
Hide Arm/Group Description Participants were randomized to receive SOF+RBV for 12 weeks. SOF was administered as a 400 mg tablet orally once daily. RBV was administered as 200 mg tablets (1000-1200 mg daily based on weight) according to package insert recommendations. Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Placebos were administered in the same manner as their active counterparts.
All-Cause Mortality
SOF+RBV Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
SOF+RBV Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   11/207 (5.31%)   2/71 (2.82%) 
Gastrointestinal disorders     
Pancreatitis  1  0/207 (0.00%)  1/71 (1.41%) 
General disorders     
Drug withdrawal syndrome  1  1/207 (0.48%)  0/71 (0.00%) 
Non-cardiac chest pain  1  1/207 (0.48%)  0/71 (0.00%) 
Oedema peripheral  1  1/207 (0.48%)  0/71 (0.00%) 
Pyrexia  1  1/207 (0.48%)  0/71 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  0/207 (0.00%)  1/71 (1.41%) 
Immune system disorders     
Hypersensitivity  1  1/207 (0.48%)  0/71 (0.00%) 
Infections and infestations     
Abdominal abscess  1  1/207 (0.48%)  0/71 (0.00%) 
Bronchitis  1  0/207 (0.00%)  1/71 (1.41%) 
Cellulitis  1  1/207 (0.48%)  0/71 (0.00%) 
Injury, poisoning and procedural complications     
Overdose  1  2/207 (0.97%)  0/71 (0.00%) 
Fall  1  1/207 (0.48%)  0/71 (0.00%) 
Injury  1  1/207 (0.48%)  0/71 (0.00%) 
Road traffic accident  1  1/207 (0.48%)  0/71 (0.00%) 
Spinal compression fracture  1  1/207 (0.48%)  0/71 (0.00%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/207 (0.48%)  0/71 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic neoplasm malignant  1  1/207 (0.48%)  0/71 (0.00%) 
Psychiatric disorders     
Abnormal behaviour  1  1/207 (0.48%)  0/71 (0.00%) 
Skin and subcutaneous tissue disorders     
Eczema  1  1/207 (0.48%)  0/71 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF+RBV Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   184/207 (88.89%)   55/71 (77.46%) 
Blood and lymphatic system disorders     
Anaemia  1  27/207 (13.04%)  0/71 (0.00%) 
Gastrointestinal disorders     
Nausea  1  46/207 (22.22%)  13/71 (18.31%) 
Diarrhoea  1  19/207 (9.18%)  4/71 (5.63%) 
Vomiting  1  12/207 (5.80%)  5/71 (7.04%) 
Abdominal pain  1  6/207 (2.90%)  4/71 (5.63%) 
General disorders     
Fatigue  1  91/207 (43.96%)  17/71 (23.94%) 
Irritability  1  19/207 (9.18%)  1/71 (1.41%) 
Oedema peripheral  1  4/207 (1.93%)  4/71 (5.63%) 
Metabolism and nutrition disorders     
Decreased appetite  1  7/207 (3.38%)  7/71 (9.86%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  16/207 (7.73%)  1/71 (1.41%) 
Nervous system disorders     
Headache  1  43/207 (20.77%)  14/71 (19.72%) 
Dizziness  1  19/207 (9.18%)  5/71 (7.04%) 
Psychiatric disorders     
Insomnia  1  39/207 (18.84%)  3/71 (4.23%) 
Anxiety  1  13/207 (6.28%)  4/71 (5.63%) 
Depression  1  15/207 (7.25%)  1/71 (1.41%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  19/207 (9.18%)  1/71 (1.41%) 
Cough  1  11/207 (5.31%)  2/71 (2.82%) 
Oropharyngeal pain  1  5/207 (2.42%)  4/71 (5.63%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  23/207 (11.11%)  6/71 (8.45%) 
Rash  1  18/207 (8.70%)  6/71 (8.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
EMail: ClinicalTrialDisclosures@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01542788    
Other Study ID Numbers: GS-US-334-0107
First Submitted: February 17, 2012
First Posted: March 2, 2012
Results First Submitted: January 6, 2014
Results First Posted: February 17, 2014
Last Update Posted: May 19, 2014